Neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1 in rats / 国际脑血管病杂志

ABSTRACT

Objective To investigate the neuroprotective effect of sophocarpine against transient focal cerebral ischemia via down-regulation of the acid-sensing ion channel 1(ASICl) in rats.Methods Twenty-five SD rats were randomly allocated into sham operation,cerebral ischemia/reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups (n=5 in each group).A rat focal ischemia model was induced by the intraluminal suture method.Five,10 and 20 mg/kg sophocarpine were injected intraperitoneally for pretreatrnent.2,3,5-triphenyltetrazolium chloride staining was used to detect cerebral infarct volume.TUNEL staining was used to detect apoptosis.Immunohistochemistry and Western blot were used to detect the expression of ASIC1 and ASIC2.Results The infarct volume after ischemia-reperfusion was(181.21±9.21)mm3,while the 5,10,and 20 mg/kg sophocarpine pretreatment groups were(150.12±6.19),(52.31±4.20),and(32.18±3.82)mm3,respectively;the neurological function scores in the cerebral ischemia/reperfusion group was(3.62±0.36),while the 5,10,and 20 mg/kg sophocarpine pretreatment grows were(3.15±0.36),(1.92±0.18),and(1.85±0.21),respectively;The surviving neurons only accounted for(31.2±2.8)% of the total cell number in the cerebral ischemia-reperfusion group,while they accounted for(51.2±3.7)%,(76.5±2.1)%,and(77.1±4.1)% in the 5,10,and 20 mg/kg sophocarpine pretreatnmat groups.Compared with the cerebral ischemia/reperfusion group,the cerebral infarct volume was decreased significantly in the sophocarpine pretreatrnent groups(all P<0.01),the neurological function scores were decreased significantly(all P<0.01),and the number of apoptotic cells was decreased significantly (all P<0.01).Immunohistochemistry showed that the number of ASIC-1 positive cells in the sham operation,cerebral ischemia-reperfusion,and 5,10,and 20 mg/kg sophocarpine pretreatment groups were(162.5±8.3),(165.1±5.3),(138.3±7.2),(82.1±6.3),and(69.2±5.5)/mm respectively;Western blot showed that the ASIC1 protein expression was decreased sigaificantly in the 10 and 20 mg/ky sophocarpine pretreatment groups (P<0.01),while there WaS no significant difference in the ASIC2 protein expression.Condusions Sophocarpine may play a neuroprotective role for cerebral ischemia-reperfusion injury in rats via down-regulating the expression of ASIC1 protein.